Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Time to failure of first-line antiretroviral therapy or death [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Failure of CD4 percentage (CD4%) to reach a level of at least 20% by Week 24 of therapy (initial therapy or restart) or CD4% falls below 20% on two occasions, within 4 weeks, at any time after the first 24 weeks of therapy (initial therapy or restart) [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Development of toxicity requiring more than one drug substitution within the same class or a switch to a new class of drugs (regimen-limiting toxicity failure) or requiring a permanent treatment discontinuation [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Development of severe CDC Stage B or Stage C disease, as defined in the protocol [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

For participants with a CD4 count of at least 25%, ART deferred until necessary

Drug: Abacavir sulfate

Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

ABC

Ziagen

Drug: Didanosine

Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

ddI

Videx

Drug: Efavirenz

Second Line Regimen: taken orally once daily. Dosage depends on weight. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

EFV

Stocrin

Drug: Lamivudine

First Line Regimen: 4 mg/kg taken orally twice daily

Other Names:

3TC

Epivir

Drug: Lopinavir/Ritonavir

First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Other Names:

LPV/r

Kaletra

Drug: Nevirapine

Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

NVP

Viramune

Drug: Zidovudine

First Line Regimen: 240 mg/m^2 taken orally twice daily

Other Names:

AZT

Retrovir

Experimental: 2A

For participants with a CD4 count of at least 25%, receive 40 weeks of ART until first birthday

Drug: Abacavir sulfate

Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

ABC

Ziagen

Drug: Didanosine

Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

ddI

Videx

Drug: Efavirenz

Second Line Regimen: taken orally once daily. Dosage depends on weight. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

EFV

Stocrin

Drug: Lamivudine

First Line Regimen: 4 mg/kg taken orally twice daily

Other Names:

3TC

Epivir

Drug: Lopinavir/Ritonavir

First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Other Names:

LPV/r

Kaletra

Drug: Nevirapine

Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

NVP

Viramune

Drug: Zidovudine

First Line Regimen: 240 mg/m^2 taken orally twice daily

Other Names:

AZT

Retrovir

Experimental: 3A

For participants with a CD4 count of at least 25%, receive ART for 96 weeks until second birthday

Drug: Abacavir sulfate

Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

ABC

Ziagen

Drug: Didanosine

Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

ddI

Videx

Drug: Efavirenz

Second Line Regimen: taken orally once daily. Dosage depends on weight. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

EFV

Stocrin

Drug: Lamivudine

First Line Regimen: 4 mg/kg taken orally twice daily

Other Names:

3TC

Epivir

Drug: Lopinavir/Ritonavir

First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Other Names:

LPV/r

Kaletra

Drug: Nevirapine

Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

NVP

Viramune

Drug: Zidovudine

First Line Regimen: 240 mg/m^2 taken orally twice daily

Other Names:

AZT

Retrovir

Experimental: 1B

For participants with a CD4 count less than 25%, receive continuous ART

Drug: Abacavir sulfate

Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

ABC

Ziagen

Drug: Didanosine

Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

ddI

Videx

Drug: Efavirenz

Second Line Regimen: taken orally once daily. Dosage depends on weight. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

EFV

Stocrin

Drug: Lamivudine

First Line Regimen: 4 mg/kg taken orally twice daily

Other Names:

3TC

Epivir

Drug: Lopinavir/Ritonavir

First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Other Names:

LPV/r

Kaletra

Drug: Nevirapine

Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.

Other Names:

NVP

Viramune

Drug: Zidovudine

First Line Regimen: 240 mg/m^2 taken orally twice daily

Other Names:

AZT

Retrovir

Detailed Description:

In South Africa, an estimated 250,000 infants are born to HIV-infected mothers each year. A high percentage of perinatal HIV infections are due to inadequate or absent mother-to-child transmission prophylaxis. Unfortunately, even with optimal prophylaxis, relatively large numbers of HIV-infected infants will continue to be born and will require antiretroviral therapy (ART). Determining the appropriate times for initiating and interrupting treatment to benefit long-term prognosis in infants is a significant health challenge. Evidence suggests that starting ART early during acute infection will provide long-term benefits. However, longer duration of treatment increases the chance of developing drug-resistant virus, and continuous therapy begun early leads to long-term complications in children. This study will evaluate the efficacy of two different short-course ART strategies in HIV-infected infants from South Africa.

This study will last at least 3.5 years. There are two parts to this study. In Part A, infants with a baseline CD4 percentage (CD4%) of at least 25% and HIV infection diagnosed between 6 and 12 weeks of age will be randomly assigned to one of two treatment strategy arms. Arm 2 infants will receive ART for approximately 40 weeks until their first birthday. Arm 3 infants will receive ART for approximately 96 weeks until their second birthday. Treatment in both arms of Part A will begin with first-line, continuous treatment of zidovudine, lamivudine, and lopinavir/ritonavir. Those who were initially deferred treatment in Arm 1 will be reassessed for initiation of first-line, continuous ART.

In Part B, infants with a baseline CD4% less than 25% will receive continuous ART. First-line ART will be started in Arm 1 or restarted after interruption in Arms 2 and 3 if the appropriate criteria as defined in the protocol is met. First-line treatment of zidovudine, lamivudine, and lopinavir/ritonavir will continue until infants reach a study endpoint; when this occurs, infants will then change to second-line therapy. Second-line ART will consist of didanosine, abacavir sulfate, nevirapine and efavirenz.

Follow-up visits will take place for 3.5 to 6 years, depending on time of enrollment. All infants will receive routine immunizations and cotrimoxazole (sulfamethoxazole/trimethoprim) prophylaxis from age 6 weeks until Week 40. Study visits will occur at study entry, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48; and every 12 weeks thereafter. At these visits, infants will have vital sign measurements, a physical exam, and a medical history evaluation. Blood and urine collection will occur at all study visits. Infants' parents or guardians will also be asked to complete an adherence questionnaire.

Participants enrolled in CIPRA-ZA Project 2 are encouraged to enroll in an observational substudy organized by the Wistar Institute (Dr. Luis Montaner, Principal Investigator), in conjunction with the CIPRA team. This study is entitled,"Pediatric Immune Correlates of Early Anti-HIV Therapy." The goal of this 5-year substudy is to evaluate 120 HIV infected children from the parent study twice a year and compare them to HIV uninfected age-matched controls. Children will be evaluated by (a) characterization and identification of the innate and adaptive immune reconstitution outcomes of early (9 or 21 months) therapy in infants infected with HIV at birth and (b) identification of immune correlate outcomes to clinical progression within a period of 2 to 3 years of follow-up after stopping therapy.

Eligibility

Ages Eligible for Study:

6 Weeks to 12 Weeks

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria for Infants:

NOTE: Per Letter of Amendment dated 04/04/07, Part B of this study is no longer recruiting participants. Per Letter of Amendment dated 09/16/08 Arm 1 of this study is longer recruiting.

HIV infected

Antiretroviral naive. Infants who have previously received antiretroviral drugs used to prevent mother-to-child transmission are eligible for the study.

Any acute or clinically significant medical event that would preclude participation in the study. Randomization can take place as soon as the incurrent illness has resolved if the child is still less than or equal to 12 weeks of age.

Use of investigational drugs

Require certain medications. More information on this criterion can be found in the protocol.

Inability to tolerate oral medication

Birth weight less than 2 kg (4.4 lbs)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00102960